RESUMO
Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB) in the spinal dorsal horn. Rikkunshito (RKT), a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB) in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Medula Espinal/efeitos dos fármacos , Animais , Hiperalgesia/metabolismo , Hiperalgesia/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Neuralgia/metabolismo , Neuralgia/prevenção & controle , Doenças do Sistema Nervoso Periférico/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
Plasminogen (Plg), which is the inactive form of plasmin, deficiency enhanced insulin secretion, and was associated with improved oral glucose tolerance in mice. Additionally, Plg deficiency was associated with lower dipeptidyl peptidase-4 (DPP-4) activity, and enhanced glucagons-like peptide-1 (GLP-1) expression. Plg may regulate the DPP-4 activity and the glucose metabolism.
Assuntos
Dipeptidil Peptidase 4/metabolismo , Intolerância à Glucose/sangue , Plasminogênio/deficiência , Animais , Glicemia/metabolismo , Metabolismo dos Carboidratos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Insulina/metabolismo , Secreção de Insulina , Masculino , Camundongos , Camundongos KnockoutRESUMO
Desulfurization of N,N-dimethylthioformamide (Me(2)NCHS) by hydrosilane has been achieved under photo irradiation in the presence of a methyl iron complex. The reaction sequences have been proposed, in which silyl migration from Fe to S of thioformamide triggers the cleavage of a C=S bond to give a carbene-iron complex. This intermediate was isolated and characterized by X-ray analysis.